Due to disease or trauma, surgeons need to replace bone tissue, and they can use bone grafts (autografts or allografts) or synthetic materials to replace bone during surgery. Amongst the types of synthetic materials used to replace bone, surgeons use metals (e.g. stainless steel hip or knee implants), polymers (e.g. polyethylene in acetabular cups), ceramics (e.g. hydroxyapatite as a macroporous bone graft) or inorganic-organic composites (e.g. hydroxyapatite-poly(lactic acid) composites for fixation plates). Many of these materials are not resorbable in the body (within a period appropriate to the healing period) and do not stimulate the formation of new bone around or within the implant.
One of the synthetic materials that has been developed over the past 30-40 years and can be used to replace bone is hydroxyapatite (HA, Ca10(PO4)6(OH)2). This material supports the growth of bone cells on its surface, and the formation of new bone, but it is very insoluble in the body, so can remain in the body for more than 10 years. For medical applications, hydroxyapatite is typically used as a coating, where it is subjected to high temperatures (>1500° C.) during the coating process, or as a macroporous ceramic, which contains large pores (>100 μm) and are produced by sintering the macroporous structure at high temperatures (e.g. 1200° C.)
To enhance the properties of hydroxyapatite, materials have been developed that contain small amounts of silicon or silicate ions. Silicon has been shown to play an important role in bone formation and in bone metabolism. The synthesis of a silicon-substituted hydroxyapatite material is described in WO 98/08773 and corresponding U.S. Pat. No. 6,312,468. The material comprises 0.1 to 5 wt % of silicon. The molar ratio of calcium ions to phosphorus-containing ions is 1:0.5 to 1:0.7. The most preferred silicon range is 0.5 to 1.0 wt %. On sintering, these materials were shown to be single phase compositions. Although these materials have been shown to accelerate the rate of bone healing in animal studies and in human clinical studies, these silicon-substituted materials are still very insoluble. A study by Guth et al., Key Eng. Mater., 2006, 309-311, pp. 117-120, showed that the amount of silicon released from these materials on soaking for up to 14 days only reached levels of 0.1-0.4 ppm. Micro-porous ceramic disks of SiHA samples (silicon-substituted hydroxyapatite) containing 0.8 wt % silicon, equivalent to 2.6 wt % silicate, were soaked in a solution of cell culture medium.
Hydroxyapatite ceramics are not readily soluble in the body and will not disappear over a reasonable time period (C.P.A.T. Klein et al, J. Biomed. Mater. Res., 1983, 17, 769). Suggested times for ideal complete resorption are between 1 month and 3 years, during which they would be replaced by new bone. It has also been shown that the release of calcium ions from materials such as calcium sulphate or calcium carbonate, and silicate ions from Bioglass (a CaO—SiO2—Na2O—P2O5 glass), can accelerate bone repair and/or stimulate osteoblasts (I. D. Xynos et al, Calc. Tiss. Int., 2000, 67, 321-329).
US 2005/0244449 describes the synthesis of a silicon substituted oxyapatite compound (Si—OAp) for use as a synthetic bone biomaterial either used alone or in biomaterial compositions. The silicon-substituted oxyapatite compound has the formula:Ca5(PO4)3-x(SiO4)xO(1-x)/2 where 0<x<1.0.Synthesis of this material involves heating a synthetic calcium phosphate composition that contains silicon at high temperatures in a vacuum atmosphere, which removes all of the hydroxyl groups from the structure. The product has properties very different from those of silicon-substituted hydroxyapatite.
GB 395713 describes the synthesis of a silicon-containing apatite single crystal. The process produces single crystals having individual crystal long-axis lengths from 5 to 500 μm, and more typically 20 to 200 μm. The synthesis is performed at a temperature of between 70 and 150° C., and octacalcium phosphate is used as an intermediate phase. The product contains CO3 and has a low silicon content in the range 0.4 to 2.4 wt % silicon, preferably 0.5-1% silicon. The Ca/P molar ratio is in the range 1:1.4 to 1:2, and the Ca/(P+Si) molar ratio is in the range 1:1.4 to 1:2.
EP1426066 describes the physical mixing, without reaction, of silica (SiO2), calcia (CaO) and hydroxyapatite, with typically 67% by weight of the mixture existing as silicon (within the SiO2). The three discrete oxide compounds are distributed in an organic polymer matrix. In GB 2363115, an implant material composed of porous and/or polycrystalline silicon is described. The silicon can be mixed into a calcium phosphate cement system or into a polymer, and exists as a discrete phase interspersed in a matrix of calcium phosphate.
JP-A-2002-137914 describes a hydroxyapatite containing silicate ions which is stated to have good ion exchange ability and antimicrobial activity. The powders obtained by the processes described, which were not calcined, have a ratio of Ca/(P+Si) at the stoichiometric level or higher. Carbonate ions are included in order to balance electric charge. It is believed that such powders will yield a hydroxyapatite containing a CaO phase on heating.
In Journal of Solid State Chemistry, 181 (2008) 1950-1960, Palard et al. describe the problem of achieving pure silicated hydroxyapatite without the presence of secondary phases. They prepared powders by an aqueous precipitation method, using a ratio of Ca/(P+Si) of 10/6. The powders contained carbonate. On calcination, carbonate-free apatites were obtained. Using the chemical formulaCa10(PO4)6-x(SiO4)x(OH)2-x with 0≦x≦2for the calcinated products, they report that the behaviour of the SixHA powders with x>1 was very different from that of the compositions with x≦1. In the former case two phases simultaneously appeared from 700° C. The phases were identified as apatite and alpha tricalcium phosphate.